Central Nervous System Demyelinating Disease Protection by the Human Commensal Bacteroides fragilis Depends on Polysaccharide A Expression
Central Nervous System Demyelinating Disease Protection by the Human Commensal Bacteroides fragilis Depends on Polysaccharide A Expression
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DOI：
10.4049/jimmunol.1001443
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发表时间：
2010-10-01
影响因子：
4.4
通讯作者：
Kasper, Lloyd H.
中科院分区：
文献类型：
--
作者：
Ochoa-Reparaz, Javier;Mielcarz, Daniel W.;Kasper, Lloyd H.
肠道共生菌在维持免疫稳态中的重要性越来越被人们所认识。我们最近描述了肠道菌群的改变可以影响实验性自身免疫性脑脊髓炎（EAE）（人类多发性硬化症的实验模型）中调节脱髓鞘的Foxp3(+)T（reg）细胞群。我们现在扩展了我们之前关于共生菌在中枢神经系统脱髓鞘中的作用的观察，我们证明了产生细菌荚膜多糖Ag的脆弱拟杆菌可以预防EAE。与野生型脆弱双歧杆菌的再定植维持了对EAE的抗性，而与缺乏多糖a的脆弱双歧杆菌的重新定植恢复了对EAE的敏感性。两株脆弱芽孢杆菌肠道再定殖后，观察到颈部淋巴结Foxp3(+)T（reg）细胞数量增加。在体外，用野生型易碎芽孢杆菌重组的小鼠获得的CD4(+)T细胞转化为产生il -10的Foxp3(+)T（reg）细胞的率显著提高，并提供更强的疾病保护。我们的研究结果表明，共生细菌Ags，特别是表达多糖A的脆弱杆菌，在EAE和可能的人类多发性硬化症中保护中枢神经系统脱髓鞘的重要作用。免疫学杂志，2010,18(5):4101-4108。
The importance of gut commensal bacteria in maintaining immune homeostasis is increasingly understood. We recently described that alteration of the gut microflora can affect a population of Foxp3(+)T(reg) cells that regulate demyelination in experimental autoimmune encephalomyelitis (EAE), the experimental model of human multiple sclerosis. We now extend our previous observations on the role of commensal bacteria in CNS demyelination, and we demonstrate that Bacteroides fragilis producing a bacterial capsular polysaccharide Ag can protect against EAE. Recolonization with wild type B. fragilis maintained resistance to EAE, whereas reconstitution with polysaccharide A-deficient B. fragilis restored EAE susceptibility. Enhanced numbers of Foxp3(+)T(reg) cells in the cervical lymph nodes were observed after intestinal recolonization with either strain of B. fragilis. Ex vivo, CD4(+)T cells obtained from mice reconstituted with wild type B. fragilis had significantly enhanced rates of conversion into IL-10-producing Foxp3(+)T(reg) cells and offered greater protection against disease. Our results suggest an important role for commensal bacterial Ags, in particular B. fragilis expressing polysaccharide A, in protecting against CNS demyelination in EAE and perhaps human multiple sclerosis. The Journal of Immunology, 2010, 185: 4101-4108.